Pulmonary surfactant is a complex mixture of phospholipids, cholesterol and proteins which lines the alveoli, lowers surface tension, and prevents alveolar collapse. Deficiency of surfactant is the primary course of respiratory distress syndrome of the newborn and abnormalities of surfactant have been observed in the adult respiratory distress syndrome. The purpose of this proposal is to study the regulation of genes encoding three surfactant specific proteins. These surfactant proteins are SP-A, a 26-36 kDa glycoprotein; SP-B, a hydrophobic protein with an unreduced molecular weight of 18 kDa; and SP-C, a hydrophobic protein with an unreduced molecular weight of 10 kDa. These proteins have key roles in determining the structural and physical properties of surfactant and are required for normal surfactant function in vivo. Surfactant proteins are also important in regulating the secretion and recycling of surfactant. However, little is known about the mechanisms which regulate their synthesis in normal and diseased lung. The goals of this research are to determine the primary structure of each protein for rat, to determine which cells in the lung synthesize each protein, and to investigate the regulation of synthesis of each protein in isolated alveolar type II epithelial cells and in vivo. The ultimate goal of this research is to understand the molecular events which regulate the production of these proteins and account for their tissue specific expression. Such knowledge may result in rational therapy directed towards modifying the expression of surfactant proteins in pulmonary diseases such as the respiratory distress syndrome and alveolar proteinosis.